Cell cell adhesion..... Learning........

Cell adhesion notes

1. Cell-cell Adhesion Dr. Tripti Singh School of Biosciences

2. Cell-cell adhesion Cell adhesion is the ability of a single cell to stick to another cell or an extracellular matrix (ECM). Cell adhesion molecules are proteins that help cell stick to each other and to the surroundings. Adhesion plays an integral role in cell communication and regulation, and is of fundamental importance in the development and maintenance of tissues.

3. Continue.. Cell adhesion is involved in stimulating signals that regulate cell differentiation, cell cycle, cell migration, and cell survival. According to the “cell adhesion model”, the more a cell sticks the more it shows the greater number of chemical bonds it has on its surface.

4. Continue… Changes in cell adhesion can be the defining event in a wide range of diseases including arthritis, atherosclerosis, osteoporosis, and cancer . Cell adhesiveness is generally reduced in human cancers. Reduced intercellular adhesiveness allows cancer cells to disobey the social order, resulting in destruction of histological structure, which may be related to the invasive and metastatic potential.

5. Importance cell adhesion It is important for: Tissue formation during morphogenesis cell migration Regulation of : cell proliferation, gene expression and cell death (apoptosis)

6. Integral membrane protein parts: Integral membrane protein embedded in the phospholipid bilayer , and has free major portions. The portion of the protein that spends the membrane, called trans- membrane region (TMR). The extracellular domain of the protein (ECD). The intracellular domain of the protein (ICD).

7. Integral membrane protein

8. Types of cell adhesion molecules (CAMs) binding: Homophilic binding: If the cell adhesion molecules between two neighboring cells are the identical. ( Cadherin-Cadherin ) Hetrophilic binding : If the cell adhesion molecules between two neighboring cell are not identical. ( Selectin- Mucin )

9. Cell adhesion molecules 1.Immunoglobulin super family cell adhesion molecules 2.Integrin 3.Selectin 4.Cadherin

10. CELL ADHESION MOLECULES Immunoglobulin super family cell adhesion molecules ( IgSF CAMs): Structure: The trans-membrane region of all the IgSF -CAMs is a single alpha helix span the membrane. (one protein) Inside and outside we have extracellular domain

11. Example: 1.Intercellular adhesion molecule-1 (ICAM-1): It is expressed in the apical membrane of endothelial cells (mainly capillary and post capillary venues). When there is an invading pathogen, the endothelial cells become activated and will express ICAM-1 on their surfaces. ICAM-1 will bind to cell adhesion molecule LFA-1 (Lymphocyte function associated -1, Integrin molecule) expressed on monocytes . Monocytes will move across the endothelial cells to the interstitial space to differentiate to macrophage.

12. Vascular cell adhesion molecule-1 (VCAM-1): Its is expressed in the apical membrane of endothelial cells. When there is an invading pathogen, the endothelial cells become activated and will express VCAM-1 on their surfaces. VCAM-1 will bind to cell adhesion molecule VLA-4 (very late antigen-4, Integrin molecule) expressed on monocytes . Monocytes will move across the endothelial cells to the interstitial space to differentiate to macrophage.

13. Platelet endothelial cell adhesion-1 (PCAM-1)= CD31: Endothelial cells posses three types of junctions: I.Tight junction II.Adherent junction III.Two PCAM-1 protein on the opposing endothelial cell membranes. ( Homophilic binding )

14. Integrin 2.Integrin: Structure: The protein is formed of two subunits, α and β subunit. there are 18 α and 8 β subunit type, however, only 24 types found in human body ) Has a large extracellular domain. Single membrane spanning α helix. A very small intracellular domain.

15. Example: 1.Lymphocyte function-associated antigen–1(LFA-1 ): LFA-1= α11 β2 = α L β2 Found on the surface of all leucocytes and mainly on the monocyte . In the inflammatory state, the endothelial cells starts to express the ICAM-1 on its surface to bind to LFA-1 of the monocytes > differentiate to macrophage in the interstitial space. 2.Very late antigen-4 (VLA-4): VLA-4 = α4 β1 Found on the surface of the monocyte . In the inflammatory state, VLA-4 binds to VCAM-1.

16. 3.Integrin bind directly to collagen: α1 β1 α2 β1 4.Integrin bind indirectly to collagen: First bind to Fibronectin α5 β1

17. Cadherin 3 .Cadherin superfamily : Extra cellular cadherin domain range from (1-34) domains. All cadherin are a trans membrane protein except T- cadherin . Types of Cadherin : 1.Type I classical cadherin 2.Type II a typical cadherin 3.Truncated cadherin 4.Desmosomal cadherin 5.Flamingo cadherin 6.Proto cadherin 7.Others

18. Types of Cadherin : 1. T- cadherin is completely outside the cell membrane and attached to it by a lipid called Glycosyl phosphatidylinositol (GPI). 2.Type I classical cadherin : It produce cell to cell direct connection. (Adherent Junction) Example: E- Cadherin : found in the epithelial cells N - Cadherin : found in the neuron, muscle tissue P - Cadherin : found in the placenta, epidermis

19. Structure: They all have 5 extracellular cadherin domain ended with amino terminal NH2. The N terminal of the Extra cadherin domain will bind to the neighboring N terminal of the EC domain. The binding is dependent to the extra cellular Ca ions.

20. 3.Desmosomal Cadherin : Types: Desmocollin (1,2,3) and Desmoglein (1,2,3,4) Structure: They all have 5 extracellular cadherin domain ended with NH2. (1 E anchor domain and 4 EC domains distally). The N terminal of the Extra cadherin domain will bind to the neighboring N terminal of the EC domain. The cytoplasmic terminal end binds to 2 proteins: 1.Plakoglobin= γ catenin 2.Plakophilin These two proteins will bind to desmoplakin intermediate filament (Keratin) The binding is dependent to the extra cellular Ca ions.

21. The extracellular core allows water and ions flow in between the cells. E.g : Skin, Intestins

22. Selectin Selectins : Example: 1.P- Selectin : Found on the endothelial cells to help the recruitment of the neutrophils , P- Selectin glycoprotein ligand 1, type 1 activation (induced by histamine and induced in minutes) . 2.E-Selectin: Found on the endothelial cells and binds to Sialyl -Lewis X found always on the surface of the neutrophil type 2 activation (takes hours).

23. L- Selectin : The high endothelial cells allows the naïve T lymphocytes to move from the blood into lymph nodes and back out. Naïve T-lymphocytes have on their surface the L- Selectin that binds to GLYCAM-1 on the high endothelial cells movement of the lymphocyte to the Lymph node.